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Reduced myelinated nerve fibre and endoneurial capillary densities in the forearm of diabetic and non-diabetic patients with carpal tunnel syndrome

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Abstract

The underlying basis of carpal tunnel syndrome (CTS) and the basis of its increased incidence in diabetes are unknown. We have quantified pathology in an uncompressed nerve (posterior interosseous nerve, PIN) in the forearm between diabetic and non-diabetic patients with CTS and control subjects. In an age- and gender-matched series, 26 diabetic patients with CTS and 20 non-diabetic patients with CTS underwent biopsy of the PIN at the time of surgical carpal tunnel release. Control subjects consisted of ten PIN biopsies taken postmortem and three biopsies taken at the time of wrist surgery. We found PIN myelinated nerve fibre density significantly reduced in diabetic (mean 5,373/mm2 [95% confidence interval, 4,835–5,911]) and non-diabetic (6,617/mm2 [5,697–7,537]) patients with CTS compared to control subjects (9,109/mm2 [7,967–10,250], P < 0.001). Furthermore, diabetic patients had a significantly lower density than non-diabetic patients (P < 0.03). Endoneurial capillary density was also reduced in diabetic (58/mm2 [50–66]) and non-diabetic (67/mm2 [55–78]) patients compared to control subjects (86/mm2 [72–101], P < 0.02) with no difference between diabetic and non-diabetic patients with CTS. Our results suggest that a reduction in myelinated nerve fibre and capillary densities may predispose patients, particularly those with diabetes, to develop CTS.

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Abbreviations

CTS:

Carpal tunnel syndrome

PIN:

Posterior interosseous nerve

SD:

Standard deviation

References

  1. Allampallam K, Chakraborty J, Bose KK, Robinson J (1996) Explant culture, immunofluorescence and electron-microscopic study of flexor retinaculum in carpal tunnel syndrome. J Occup Environ Med 38:264–271

    Article  CAS  PubMed  Google Scholar 

  2. Atroshi I, Gummesson C, Johnsson R, Ornstein E, Ranstam J, Rosen I (1999) Prevalence of carpal tunnel syndrome in a general population. JAMA 282:153–158

    Article  CAS  PubMed  Google Scholar 

  3. Atroshi I, Hofer M, Larsson GU, Ornstein E, Johnsson R, Ranstam J (2009) Open compared with 2-portal endoscopic carpal tunnel release: a 5-year follow-up of a randomized controlled trial. J Hand Surg Am 34:266–272

    Article  PubMed  Google Scholar 

  4. Becker J, Nora DB, Gomes I et al (2002) An evaluation of gender, obesity, age and diabetes mellitus as risk factors for carpal tunnel syndrome. Clin Neurophysiol 113:1429–1434

    Article  PubMed  Google Scholar 

  5. Brownlee M, Cerami A, Vlassara H (1988) Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 318:1315–1321

    CAS  PubMed  Google Scholar 

  6. Chammas M, Bousquet P, Renard E, Poirier JL, Jaffiol C, Allieu Y (1995) Dupuytren’s disease, carpal tunnel syndrome, trigger finger, and diabetes mellitus. J Hand Surg Am 20:109–114

    Article  CAS  PubMed  Google Scholar 

  7. Chaudhry V, Stevens JC, Kincaid J, So YT (2006) Practice Advisory: utility of surgical decompression for treatment of diabetic neuropathy: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 66:1805–1808

    Article  PubMed  Google Scholar 

  8. Chaudhuri KR, Davidson AR, Morris IM (1989) Limited joint mobility and carpal tunnel syndrome in insulin-dependent diabetes. Br J Rheumatol 28:191–194

    Article  CAS  PubMed  Google Scholar 

  9. Comi G, Lozza L, Galardi G, Ghilardi MF, Medaglini S, Canal N (1985) Presence of carpal tunnel syndrome in diabetics: effect of age, sex, diabetes duration and polyneuropathy. Acta Diabetol Lat 22:259–262

    Article  CAS  PubMed  Google Scholar 

  10. Dahlin LB, Meiri KF, McLean WG, Rydevik B, Sjostrand J (1986) Effects of nerve compression on fast axonal transport in streptozotocin-induced diabetes mellitus. An experimental study in the sciatic nerve of rats. Diabetologia 29:181–185

    Article  CAS  PubMed  Google Scholar 

  11. Dahlin LB, Nordborg C, Lundborg G (1987) Morphologic changes in nerve cell bodies induced by experimental graded nerve compression. Exp Neurol 95:611–621

    Article  CAS  PubMed  Google Scholar 

  12. Dahlin LB, Stenberg L, Luthman H, Thomsen NO (2008) Nerve compression induces activating transcription factor 3 in neurons and Schwann cells in diabetic rats. Neuroreport 19:987–990

    Article  CAS  PubMed  Google Scholar 

  13. Dyck PJ, Kratz KM, Karnes JL et al (1993) The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology 43:817–824

    CAS  PubMed  Google Scholar 

  14. England JD, Gronseth GS, Franklin G et al (2005) Distal symmetric polyneuropathy: a definition for clinical research: report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 64:199–207

    CAS  PubMed  Google Scholar 

  15. Hirata H, Nagakura T, Tsujii M, Morita A, Fujisawa K, Uchida A (2004) The relationship of VEGF and PGE2 expression to extracellular matrix remodelling of the tenosynovium in the carpal tunnel syndrome. J Pathol 204:605–612

    Article  CAS  PubMed  Google Scholar 

  16. Jakobsen J (1978) Peripheral nerves in early experimental diabetes: expansion of the endoneurial space as a cause of increased water content. Diabetologia 14:113–119

    Article  CAS  PubMed  Google Scholar 

  17. Jakobsen J, Sidenius P (1980) Decreased axonal transport of structural proteins in streptozotocin diabetic rats. J Clin Invest 66:292–297

    Article  CAS  PubMed  Google Scholar 

  18. Jung Y, Hohmann TC, Gerneth JA et al (1971) Diabetic hand syndrome. Metabolism 20:1008–1015

    Article  CAS  PubMed  Google Scholar 

  19. Llewelyn JG, Gilbey SG, Thomas PK, King RH, Muddle JR, Watkins PJ (1991) Sural nerve morphometry in diabetic autonomic and painful sensory neuropathy. A clinicopathological study. Brain 114(Pt 2):867–892

    Article  PubMed  Google Scholar 

  20. Low PA (1987) Recent advances in the pathogenesis of diabetic neuropathy. Muscle Nerve 10:121–128

    Article  CAS  PubMed  Google Scholar 

  21. Malik RA, Tesfaye S, Newrick PG et al (2005) Sural nerve pathology in diabetic patients with minimal but progressive neuropathy. Diabetologia 48:578–585

    Article  CAS  PubMed  Google Scholar 

  22. Malik RA, Veves A, Walker D et al (2001) Sural nerve fibre pathology in diabetic patients with mild neuropathy: relationship to pain, quantitative sensory testing and peripheral nerve electrophysiology. Acta Neuropathol 101:367–374

    CAS  PubMed  Google Scholar 

  23. Mondelli M, Padua L, Reale F, Signorini AM, Romano C (2004) Outcome of surgical release among diabetics with carpal tunnel syndrome. Arch Phys Med Rehabil 85:7–13

    Article  PubMed  Google Scholar 

  24. Mulder DW, Lambert EH, Bastron JA, Sprague RG (1961) The neuropathies associated with diabetes mellitus. A clinical and electromyographic study of 103 unselected diabetic patients. Neurology 11(4 Pt 1):275–284

    Article  PubMed  Google Scholar 

  25. Myers RR, Murakami H, Powell HC (1986) Reduced nerve blood flow in edematous neuropathies: a biomechanical mechanism. Microvasc Res 32:145–151

    Article  CAS  PubMed  Google Scholar 

  26. Papanicolaou GD, McCabe SJ, Firrell J (2001) The prevalence and characteristics of nerve compression symptoms in the general population. J Hand Surg Am 26:460–466

    Article  CAS  PubMed  Google Scholar 

  27. Perkins BA, Olaleye D, Bril V (2002) Carpal tunnel syndrome in patients with diabetic polyneuropathy. Diabetes Care 25:565–569

    Article  PubMed  Google Scholar 

  28. Powell HC, Costello ML, Myers RR (1981) Endoneurial fluid pressure in experimental models of diabetic neuropathy. J Neuropathol Exp Neurol 40:613–624

    Article  CAS  PubMed  Google Scholar 

  29. Rempel D, Dahlin L, Lundborg G (1999) Pathophysiology of nerve compression syndromes: response of peripheral nerves to loading. J Bone Joint Surg Am 81:1600–1610

    CAS  PubMed  Google Scholar 

  30. Rosen I (1993) Neurophysiological diagnosis of the carpal tunnel syndrome: evaluation of neurographic techniques. Scand J Plast Reconstr Surg Hand Surg 27:95–101

    Article  CAS  PubMed  Google Scholar 

  31. Rosenbloom AL, Silverstein JH (1996) Connective tissue and joint disease in diabetes mellitus. Endocrinol Metab Clin North Am 25:473–483

    Article  CAS  PubMed  Google Scholar 

  32. Russell JW, Karnes JL, Dyck PJ (1996) Sural nerve myelinated fiber density differences associated with meaningful changes in clinical and electrophysiologic measurements. J Neurol Sci 135:114–117

    Article  CAS  PubMed  Google Scholar 

  33. Singh R, Gamble G, Cundy T (2005) Lifetime risk of symptomatic carpal tunnel syndrome in Type 1 diabetes. Diabet Med 22:625–630

    Article  CAS  PubMed  Google Scholar 

  34. Stevens JC, Smith BE, Weaver AL, Bosch EP, Deen HG Jr, Wilkens JA (1999) Symptoms of 100 patients with electromyographically verified carpal tunnel syndrome. Muscle Nerve 22:1448–1456

    Article  CAS  PubMed  Google Scholar 

  35. Stromberg T, Dahlin LB, Brun A, Lundborg G (1997) Structural nerve changes at wrist level in workers exposed to vibration. Occup Environ Med 54:307–311

    Article  CAS  PubMed  Google Scholar 

  36. Tankisi H, Pugdahl K, Fuglsang-Frederiksen A et al (2005) Pathophysiology inferred from electrodiagnostic nerve tests and classification of polyneuropathies. Suggested guidelines. Clin Neurophysiol 116:1571–1580

    Article  PubMed  Google Scholar 

  37. Thomas PK, Fullerton PM (1963) Nerve fibre size in the carpal tunnel syndrome. J Neurol Neurosurg Psychiatry 26:520–527

    Article  CAS  PubMed  Google Scholar 

  38. Thomsen NO, Cederlund R, Rosen I, Bjork J, Dahlin LB (2009) Clinical outcomes of surgical release among diabetic patients with carpal tunnel syndrome: prospective follow-up with matched controls. J Hand Surg Am [Epub ahead of print]

  39. Thomsen NO, Mojaddidi M, Malik RA, Dahlin LB (2009) Biopsy of the posterior interosseous nerve: a low morbidity method for assessment of peripheral nerve disorders. Diabet Med 26:100–104

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study is supported by grants from the Swedish Research Council (Medicine), Crafoord’s Fund for Medical Research, Svenska Diabetesförbundet, Diabetesföreningen Malmö, Konsul Thure Carlsson Fund for Medical Research, Region Skåne and Funds from the University Hospital Malmö, Sweden.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Hand Surgery, Malmö University Hospital, 205 02, Malmö, Sweden

    Niels O. B. Thomsen & Lars B. Dahlin

  2. Division of Cardiovascular Medicine, Manchester Royal Infirmary, University of Manchester, Oxford Road, Manchester, M13 9WL, UK

    Moaz Mojaddidi & Rayaz A. Malik

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  1. Niels O. B. Thomsen
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  2. Moaz Mojaddidi
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  3. Rayaz A. Malik
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  4. Lars B. Dahlin
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Correspondence to Niels O. B. Thomsen.

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Thomsen, N.O.B., Mojaddidi, M., Malik, R.A. et al. Reduced myelinated nerve fibre and endoneurial capillary densities in the forearm of diabetic and non-diabetic patients with carpal tunnel syndrome. Acta Neuropathol 118, 785–791 (2009). https://doi.org/10.1007/s00401-009-0578-0

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  • DOI: https://doi.org/10.1007/s00401-009-0578-0

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